CENPF
Centromerni protein F jest protein koji je kod ljudi kodiran genom CENPF sa hromosoma 1.[5][6][7] Uključen je u segregaciju hromosoma tokom ćelijske diobe. Također ima ulogu u orijentaciji mikrotubula u formiranju ćelijskih cilija.[8][9]
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 3.210 aminokiselina, a molekulska težina 367.764 Da.[10]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MSWALEEWKE | GLPTRALQKI | QELEGQLDKL | KKEKQQRQFQ | LDSLEAALQK | ||||
| QKQKVENEKT | EGTNLKRENQ | RLMEICESLE | KTKQKISHEL | QVKESQVNFQ | ||||
| EGQLNSGKKQ | IEKLEQELKR | CKSELERSQQ | AAQSADVSLN | PCNTPQKIFT | ||||
| TPLTPSQYYS | GSKYEDLKEK | YNKEVEERKR | LEAEVKALQA | KKASQTLPQA | ||||
| TMNHRDIARH | QASSSVFSWQ | QEKTPSHLSS | NSQRTPIRRD | FSASYFSGEQ | ||||
| EVTPSRSTLQ | IGKRDANSSF | FDNSSSPHLL | DQLKAQNQEL | RNKINELELR | ||||
| LQGHEKEMKG | QVNKFQELQL | QLEKAKVELI | EKEKVLNKCR | DELVRTTAQY | ||||
| DQASTKYTAL | EQKLKKLTED | LSCQRQNAES | ARCSLEQKIK | EKEKEFQEEL | ||||
| SRQQRSFQTL | DQECIQMKAR | LTQELQQAKN | MHNVLQAELD | KLTSVKQQLE | ||||
| NNLEEFKQKL | CRAEQAFQAS | QIKENELRRS | MEEMKKENNL | LKSHSEQKAR | ||||
| EVCHLEAELK | NIKQCLNQSQ | NFAEEMKAKN | TSQETMLRDL | QEKINQQENS | ||||
| LTLEKLKLAV | ADLEKQRDCS | QDLLKKREHH | IEQLNDKLSK | TEKESKALLS | ||||
| ALELKKKEYE | ELKEEKTLFS | CWKSENEKLL | TQMESEKENL | QSKINHLETC | ||||
| LKTQQIKSHE | YNERVRTLEM | DRENLSVEIR | NLHNVLDSKS | VEVETQKLAY | ||||
| MELQQKAEFS | DQKHQKEIEN | MCLKTSQLTG | QVEDLEHKLQ | LLSNEIMDKD | ||||
| RCYQDLHAEY | ESLRDLLKSK | DASLVTNEDH | QRSLLAFDQQ | PAMHHSFANI | ||||
| IGEQGSMPSE | RSECRLEADQ | SPKNSAILQN | RVDSLEFSLE | SQKQMNSDLQ | ||||
| KQCEELVQIK | GEIEENLMKA | EQMHQSFVAE | TSQRISKLQE | DTSAHQNVVA | ||||
| ETLSALENKE | KELQLLNDKV | ETEQAEIQEL | KKSNHLLEDS | LKELQLLSET | ||||
| LSLEKKEMSS | IISLNKREIE | ELTQENGTLK | EINASLNQEK | MNLIQKSESF | ||||
| ANYIDEREKS | ISELSDQYKQ | EKLILLQRCE | ETGNAYEDLS | QKYKAAQEKN | ||||
| SKLECLLNEC | TSLCENRKNE | LEQLKEAFAK | EHQEFLTKLA | FAEERNQNLM | ||||
| LELETVQQAL | RSEMTDNQNN | SKSEAGGLKQ | EIMTLKEEQN | KMQKEVNDLL | ||||
| QENEQLMKVM | KTKHECQNLE | SEPIRNSVKE | RESERNQCNF | KPQMDLEVKE | ||||
| ISLDSYNAQL | VQLEAMLRNK | ELKLQESEKE | KECLQHELQT | IRGDLETSNL | ||||
| QDMQSQEISG | LKDCEIDAEE | KYISGPHELS | TSQNDNAHLQ | CSLQTTMNKL | ||||
| NELEKICEIL | QAEKYELVTE | LNDSRSECIT | ATRKMAEEVG | KLLNEVKILN | ||||
| DDSGLLHGEL | VEDIPGGEFG | EQPNEQHPVS | LAPLDESNSY | EHLTLSDKEV | ||||
| QMHFAELQEK | FLSLQSEHKI | LHDQHCQMSS | KMSELQTYVD | SLKAENLVLS | ||||
| TNLRNFQGDL | VKEMQLGLEE | GLVPSLSSSC | VPDSSSLSSL | GDSSFYRALL | ||||
| EQTGDMSLLS | NLEGAVSANQ | CSVDEVFCSS | LQTYVDSLKA | ENLVLSTNLR | ||||
| NFQGDLVKEM | QLGLEEGLVP | SLSSSCVPDS | SSLSSLGDSS | FYRALLEQTG | ||||
| DMSLLSNLEG | VVSANQCSVD | EVFCSSLQEE | NLTRKETPSA | PAKGVEELES | ||||
| LCEVYRQSLE | KLEEKMESQG | IMKNKEIQEL | EQLLSSERQE | LDCLRKQYLS | ||||
| ENEQWQQKLT | SVTLEMESKL | AAEKKQTEQL | SLELEVARLQ | LQGLDLSSRS | ||||
| LLGIDTEDAI | QGRNESCDIS | KEHTSETTER | TPKHDVHQIC | DKDAQQDLNL | ||||
| DIEKITETGA | VKPTGECSGE | QSPDTNYEPP | GEDKTQGSSE | CISELSFSGP | ||||
| NALVPMDFLG | NQEDIHNLQL | RVKETSNENL | RLLHVIEDRD | RKVESLLNEM | ||||
| KELDSKLHLQ | EVQLMTKIEA | CIELEKIVGE | LKKENSDLSE | KLEYFSCDHQ | ||||
| ELLQRVETSE | GLNSDLEMHA | DKSSREDIGD | NVAKVNDSWK | ERFLDVENEL | ||||
| SRIRSEKASI | EHEALYLEAD | LEVVQTEKLC | LEKDNENKQK | VIVCLEEELS | ||||
| VVTSERNQLR | GELDTMSKKT | TALDQLSEKM | KEKTQELESH | QSECLHCIQV | ||||
| AEAEVKEKTE | LLQTLSSDVS | ELLKDKTHLQ | EKLQSLEKDS | QALSLTKCEL | ||||
| ENQIAQLNKE | KELLVKESES | LQARLSESDY | EKLNVSKALE | AALVEKGEFA | ||||
| LRLSSTQEEV | HQLRRGIEKL | RVRIEADEKK | QLHIAEKLKE | RERENDSLKD | ||||
| KVENLERELQ | MSEENQELVI | LDAENSKAEV | ETLKTQIEEM | ARSLKVFELD | ||||
| LVTLRSEKEN | LTKQIQEKQG | QLSELDKLLS | SFKSLLEEKE | QAEIQIKEES | ||||
| KTAVEMLQNQ | LKELNEAVAA | LCGDQEIMKA | TEQSLDPPIE | EEHQLRNSIE | ||||
| KLRARLEADE | KKQLCVLQQL | KESEHHADLL | KGRVENLERE | LEIARTNQEH | ||||
| AALEAENSKG | EVETLKAKIE | GMTQSLRGLE | LDVVTIRSEK | ENLTNELQKE | ||||
| QERISELEII | NSSFENILQE | KEQEKVQMKE | KSSTAMEMLQ | TQLKELNERV | ||||
| AALHNDQEAC | KAKEQNLSSQ | VECLELEKAQ | LLQGLDEAKN | NYIVLQSSVN | ||||
| GLIQEVEDGK | QKLEKKDEEI | SRLKNQIQDQ | EQLVSKLSQV | EGEHQLWKEQ | ||||
| NLELRNLTVE | LEQKIQVLQS | KNASLQDTLE | VLQSSYKNLE | NELELTKMDK | ||||
| MSFVEKVNKM | TAKETELQRE | MHEMAQKTAE | LQEELSGEKN | RLAGELQLLL | ||||
| EEIKSSKDQL | KELTLENSEL | KKSLDCMHKD | QVEKEGKVRE | EIAEYQLRLH | ||||
| EAEKKHQALL | LDTNKQYEVE | IQTYREKLTS | KEECLSSQKL | EIDLLKSSKE | ||||
| ELNNSLKATT | QILEELKKTK | MDNLKYVNQL | KKENERAQGK | MKLLIKSCKQ | ||||
| LEEEKEILQK | ELSQLQAAQE | KQKTGTVMDT | KVDELTTEIK | ELKETLEEKT | ||||
| KEADEYLDKY | CSLLISHEKL | EKAKEMLETQ | VAHLCSQQSK | QDSRGSPLLG | ||||
| PVVPGPSPIP | SVTEKRLSSG | QNKASGKRQR | SSGIWENGRG | PTPATPESFS | ||||
| KKSKKAVMSG | IHPAEDTEGT | EFEPEGLPEV | VKKGFADIPT | GKTSPYILRR | ||||
| TTMATRTSPR | LAAQKLALSP | LSLGKENLAE | SSKPTAGGSR | SQKVKVAQRS | ||||
| PVDSGTILRE | PTTKSVPVNN | LPERSPTDSP | REGLRVKRGR | LVPSPKAGLE | ||||
| SNGSENCKVQ |
Funkcija
[uredi | uredi izvor]CENPF je dio jedarnog matriksa tokom G2-faze ćelijskog ciklusa (faza brze sinteze proteina u pripremi za mitozu). U kasnoj G2, protein čini dio kinetohorskog, proteinskog kompleksa u obliku diska koji omogućava centromerama dviju sestrinskih hromatida da se veže za mikrotubule (formirajući aparat vretena) kako bi ih mikrotubule razdvojile u procesu ćelijske diobe. Ostaje dio kinetohora tokom rane anafaze (faza podjele hromosoma). U kasnoj anafazi, CENPF odlazi na srednju zonu vretena, a u telofazi (faza dijeljenja ćelija) sdolazi na međućelijski most. Smatra se da se naknadno degradira. Mutacije u "CENPF" dovode do poremećene diobe ćelija tokom ranog razvoja. Utvrđeno je da mitozaa traje duže kada je gen mutiran.[8][9]
Mikrotubule su proteinske strukture koje su dio citoskeleta i neophodne su kako bi ćelije imale različite, složene oblike i sposobnost migraciona. Njih pravi centrosom, koji sadrži par cilindričnih centriola pod pravim uglom jedna u odnosu na drugu. Prije podjele, CENPF se lokalizira na kraju jedne od centriola (matične centriole), kako bi ispravno orijentirao mikrotubule u formiranju tankih ćelijskih projekcija koje se nazivaju cilije. Većina cilija su primarne cilije, koje su uključene u ćelijsku signalizaciju da bi pokrenule migraciju, diobu ili diferencijaciju. Mutacije u "CENPF" remete ovu sposobnost formiranja cilija; utvrđeno je da su cilije malobrbrojnije i kraće kada je gen mutiran.[8][11]
Smatra se da CENPF formira ili homodimer ili heterodimer.
Klinički značaj
[uredi | uredi izvor]Mutacije u obje kopije CENPF uzrokuju Strømmeov sindrom, karakteriziran mikrocefalijom, abnormalnostima očne jabučice i jejunumskom atrezijom.[9] Autoantitijela protiv CENPF-a pronađena bolesti u kod pacijenata s rakom ili bolesti reakcije transplantata protiv domaćina.[7]
Također pogledajte
[uredi | uredi izvor]Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000117724 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026605 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Rattner JB, Rao A, Fritzler MJ, Valencia DW, Yen TJ (Mar 1994). "CENP-F is a .ca 400 kDa kinetochore protein that exhibits a cell-cycle dependent localization". Cell Motil Cytoskeleton. 26 (3): 214–26. doi:10.1002/cm.970260305. PMID 7904902.
- ^ Testa JR, Zhou JY, Bell DW, Yen TJ (Mar 1995). "Chromosomal localization of the genes encoding the kinetochore proteins CENPE and CENPF to human chromosomes 4q24→q25 and 1q32→q41, respectively, by fluorescence in situ hybridization". Genomics. 23 (3): 691–3. doi:10.1006/geno.1994.1558. PMID 7851898.
- ^ a b "Entrez Gene: CENPF centromere protein F, 350/400ka (mitosin)".
- ^ a b c Waters, Aoife M.; Asfahani, Rowan; Carroll, Paula; Bicknell, Louise; Lescai, Francesco; Bright, Alison; Chanudet, Estelle; Brooks, Anthony; Christou-Savina, Sonja; Osman, Guled; Walsh, Patrick (mart 2015). "The kinetochore protein, CENPF, is mutated in human ciliopathy and microcephaly phenotypes". Journal of Medical Genetics. 52 (3): 147–156. doi:10.1136/jmedgenet-2014-102691. ISSN 1468-6244. PMC 4345935. PMID 25564561.
- ^ a b c Filges, Isabel; Bruder, Elisabeth; Brandal, Kristin; Meier, Stephanie; Undlien, Dag Erik; Waage, Trine Rygvold; Hoesli, Irene; Schubach, Max; de Beer, Tjaart; Sheng, Ying; Hoeller, Sylvia (april 2016). "Strømme Syndrome Is a Ciliary Disorder Caused by Mutations in CENPF". Human Mutation. 37 (4): 359–363. doi:10.1002/humu.22960. ISSN 1098-1004. PMID 26820108. S2CID 1495539.
- ^ "UniProt, P49454" (jezik: en.). Pristupljeno 8. 12. 2021.CS1 održavanje: nepoznati jezik (link)
- ^ "OMIM Entry - # 243605 - STROMME SYNDROME; STROMS". www.omim.org (jezik: engleski). Pristupljeno 27. 9. 2018.
Dopunska literatura
[uredi | uredi izvor]- Ma L, Zhao X, Zhu X (2006). "Mitosin/CENP-F in mitosis, transcriptional control, and differentiation". J. Biomed. Sci. 13 (2): 205–13. doi:10.1007/s11373-005-9057-3. PMID 16456711.
- Liao H, Winkfein RJ, Mack G, et al. (1995). "CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis". J. Cell Biol. 130 (3): 507–18. doi:10.1083/jcb.130.3.507. PMC 2120529. PMID 7542657.
- Li Q, Ke Y, Kapp JA, et al. (1995). "A novel cell-cycle-dependent 350-kDa nuclear protein: C-terminal domain sufficient for nuclear localization". Biochem. Biophys. Res. Commun. 212 (1): 220–8. doi:10.1006/bbrc.1995.1959. PMID 7612011.
- Zhu X, Chang KH, He D, et al. (1995). "The C terminus of mitosin is essential for its nuclear localization, centromere/kinetochore targeting, and dimerization". J. Biol. Chem. 270 (33): 19545–50. doi:10.1074/jbc.270.33.19545. PMID 7642639.
- Zhu X, Mancini MA, Chang KH, et al. (1995). "Characterization of a novel 350-kilodalton nuclear phosphoprotein that is specifically involved in mitotic-phase progression". Mol. Cell. Biol. 15 (9): 5017–29. doi:10.1128/MCB.15.9.5017. PMC 230749. PMID 7651420.
- Li S, Ku CY, Farmer AA, et al. (1998). "Identification of a novel cytoplasmic protein that specifically binds to nuclear localization signal motifs". J. Biol. Chem. 273 (11): 6183–9. doi:10.1074/jbc.273.11.6183. PMID 9497340.
- Chan GK, Schaar BT, Yen TJ (1998). "Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1". J. Cell Biol. 143 (1): 49–63. doi:10.1083/jcb.143.1.49. PMC 2132809. PMID 9763420.
- Zhu X (1999). "Structural requirements and dynamics of mitosin-kinetochore interaction in M phase". Mol. Cell. Biol. 19 (2): 1016–24. doi:10.1128/MCB.19.2.1016. PMC 116032. PMID 9891037.
- Erlanson M, Casiano CA, Tan EM, et al. (1999). "Immunohistochemical analysis of the proliferation associated nuclear antigen CENP-F in non-Hodgkin's lymphoma". Mod. Pathol. 12 (1): 69–74. PMID 9950165.
- Goodwin RL, Pabón-Peña LM, Foster GC, Bader D (1999). "The cloning and analysis of LEK1 identifies variations in the LEK/centromere protein F/mitosin gene family". J. Biol. Chem. 274 (26): 18597–604. doi:10.1074/jbc.274.26.18597. PMID 10373470.
- Ashar HR, James L, Gray K, et al. (2000). "Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules". J. Biol. Chem. 275 (39): 30451–7. doi:10.1074/jbc.M003469200. PMID 10852915.
- Kobayashi M, Hanai R (2001). "M phase-specific association of human topoisomerase IIIbeta with chromosomes". Biochem. Biophys. Res. Commun. 287 (1): 282–7. doi:10.1006/bbrc.2001.5580. PMID 11549288.
- Hussein D, Taylor SS (2003). "Farnesylation of Cenp-F is required for G2/M progression and degradation after mitosis". J. Cell Sci. 115 (Pt 17): 3403–14. doi:10.1242/jcs.115.17.3403. PMID 12154071.
- Holstein SA, Hohl RJ (2003). "Synergistic interaction of lovastatin and paclitaxel in human cancer cells". Mol. Cancer Ther. 1 (2): 141–9. PMID 12467231.
- Konstantinidou AE, Korkolopoulou P, Kavantzas N, et al. (2003). "Mitosin, a novel marker of cell proliferation and early recurrence in intracranial meningiomas". Histol. Histopathol. 18 (1): 67–74. PMID 12507285.
- Yang ZY, Guo J, Li N, et al. (2004). "Mitosin/CENP-F is a conserved kinetochore protein subjected to cytoplasmic dynein-mediated poleward transport". Cell Res. 13 (4): 275–83. doi:10.1038/sj.cr.7290172. PMID 12974617.
- Laoukili J, Kooistra MR, Brás A, et al. (2005). "FoxM1 is required for execution of the mitotic programme and chromosome stability". Nat. Cell Biol. 7 (2): 126–36. doi:10.1038/ncb1217. PMID 15654331. S2CID 11732068.
- Zhou X, Wang R, Fan L, et al. (2005). "Mitosin/CENP-F as a negative regulator of activating transcription factor-4". J. Biol. Chem. 280 (14): 13973–7. doi:10.1074/jbc.M414310200. PMID 15677469.
Vanjski linkovi
[uredi | uredi izvor]- Lokacija ljudskog genoma CENPF i stranica sa detaljima o genu CENPF u UCSC Genome Browseru.